Interstitial Cystitis

Reviewing the Literature

RIU0282_08-12.qxd 8/12/06 3:08 PM Page 169 REVIEWING THE LITERATURE News and Views from the Literature Interstitial Cystitis Disappointing News for Urologists Managing Interstitial Cystitis Patients Reviewed by J. Curtis Nickel, MD, FRCSC Department of Urology, Queen’s University, Kingston, Ontario, Canada [Rev Urol. 2006;8(3):169-170] © 2006 MedReviews, LLC ata supporting effective therapies for interstitial cystitis (IC) are scarce. The year 2005 started out with so much promise. Reports were going to be published that would announce the results of 3 promising intravesical therapies: alkalinization, Bacillus CalmetteGuérin (BCG), and resiniferatoxin (RTX). But the promises of these novel, exciting approaches to the management of IC were dashed against the bulwarks of evidence from randomized, placebo-controlled trials. D A Prospective, Double-Blind, Randomized Cross-Over Study Evaluating Changes in Urinary pH for Relieving the Symptoms of Interstitial Cystitis Nguan C, Franciosi LG, Butterfield NN, et al. BJU Int. 2005;95:91-94. Alkalinizing agents have been advocated and used for decades to ameliorate the symptoms of IC. Preclinical work in anaesthesia, pharmacology, and the neurosciences has shown that neural modulation and transmission of pain are accentuated in low-pH environments. To provide evidence for the clinical efficacy of changing urinary pH on the pain associated with IC, Nguan and colleagues randomized 26 women with IC to crossover instillations of urine at physiological pH (pH 5.0) and neutral buffered pH (pH 7.5). The outcome measured was the short-term subjective symptom of pain, assessed with a visual analogue scale at baseline, after the initial instillation, at washout, and after crossover instillation. There were no statistically significant differences between baseline pain scores (or other secondary outcomes) and scores after the instillation of neutral buffered solution compared with acidic solution. Although these results are disheartening, further work should continue to determine the long-term benefits of oral buffer administration in patients with IC. A Randomized Controlled Trial of Intravesical Bacillus Calmette-Guérin for Treatment Refractory Interstitial Cystitis Mayer R, Propert KJ, Peters KM, et al. J Urol. 2005;173:1186-1191. A number of small pilot studies (uncontrolled and randomized placebo controlled) have suggested that instillation of BCG might benefit patients with IC. The cause of IC has been postulated to be a dysregulation or imbalance of the local immune system, and BCG stimulates the appropriate cytokine profile that could theoretically benefit IC-associated inflammation. A multicenter, double-blind, randomized, placebo-controlled clinical trial was designed by the National Institutes of Health Interstitial Cystitis Clinical Trials Group to determine the safety and efficacy of intravesical BCG in patients with chronic treatmentrefractory IC. A total of 265 IC patients were randomized VOL. 8 NO. 3 2006 REVIEWS IN UROLOGY 169 RIU0282_08-12.qxd 8/12/06 3:08 PM Page 170 Kidney Stones continued to 6 weekly double-blinded intravesical instillations of either BCG or placebo and followed for a total of 34 weeks. The response rate for the primary outcome (patient-reported global response questionnaire) was 12% for placebo and 21% for BCG (P
.06). The BCG safety profile in IC patients was acceptable. Unfortunately the response rate was low, and this modality of therapy could not be recommended for general use in IC patients. Intravesical Resiniferatoxin for the Treatment of Interstitial Cystitis: A Randomized, DoubleBlind, Placebo Controlled Trial Payne CK, Mosbaugh PG, Forrest JB, et al. J Urol. 2005;173:1590-1594. Interest in using vanilloid compounds for intravesical therapy in IC is based on mechanisms of pain development (C-fiber hypersensitivity) and evidence from a number of clinical pilot studies. RTX is an ultra-potent analogue of capsaicin that is believed to be safer and more effective (in terms of desensitizing bladder afferents). An ICOS-funded multicenter study group performed a randomized, doubleblind, placebo-controlled study in 163 IC patients to determine the safety and efficacy (primary outcome measured was the Global Response Assessment, similar to the outcome tool used in the BCG trial) of various doses of intravesical RTX compared with placebo. RTX did not improve overall symptoms, pain, urgency, frequency, nocturia, or average void volume during 12 weeks’ follow-up. This study demonstrated that a single administration of RTX was not effective in patients with IC. Effective therapy for IC remains elusive. Studies funded by the National Institutes of Health that are presently enrolling patients include evaluation of neuromodulation (amitriptyline) in early-diagnosed disease, immunomodulation (mycophenolate mofetil HCl [CellCept]) in late treatment-refractory disease, physical therapy, and psychosocial intervention. Kidney Stones educing urinary oxalate excretion in calcium oxalate stone formers with enteric hyperoxaluria might be difficult to accomplish. Dietary modifications, such as reduced fat and oxalate consumption, have been combined with the administration of calcium supplements and bile sequestrants like cholestyramine. However, patients might not be compliant with such regimens, and even if so, outcomes might not always be effective. R Use of a Probiotic to Decrease Hyperoxaluria Lieske JC, Goldfarb DS, De Simone C, Regner C. Kidney Int. 2005;68:1244-1249. Lieske and colleagues performed a study in which a lactic acid bacterial preparation, Oxadrop (Seaford Pharmaceuticals, Mississauga, Ontario, Canada), was administered on a daily basis for 3 months in 10 calcium oxalate stone formers with enteric hyperoxaluria due to a variety of gastrointestinal disorders causing chronic fat malabsorption. The dose of this probiotic preparation was increased each month. Twenty-four urine specimens were collected before the intervention, during each month of the intervention, and 1 month later. Mean oxalate excretion decreased by 19% at 1 month, 24% at 2 months, and returned to near baseline level at 3 months. A reduction in the supersaturation of calcium oxalate also occurred. There were no adverse events. The administration of this probiotic preparation promoted a reduction in urinary oxalate excretion and supersaturation of calcium oxalate in a group of stone formers afflicted with enteric hyperoxaluria. More than 50% of the urinary oxalate pool is derived from dietary sources. Therefore, gastrointestinal oxalate absorption has a profound influence on urinary oxalate excretion and consequently calcium oxalate supersaturation. Patients with enteric hyperoxaluria absorb oxalate more readily, and the aforementioned measures have been A lactic acid bacterial preparation was administered on a daily basis for 3 months in 10 calcium oxalate stone formers with enteric hyperoxaluria. Probiotic Therapy for Hyperoxaluria Reviewed by Dean G. Assimos, MD Department of Urology, Wake Forest University School of Medicine, Winston-Salem, NC [Rev Urol. 2006;8(3):170-171] © 2006 MedReviews, LLC 170 VOL. 8 NO. 3 2006 REVIEWS IN UROLOGY used to attenuate this response. The results of this study suggest that probiotic therapy might have beneficial effects in this group of patients. However, a number of issues need to be considered. First, the reduction in urinary oxalate excretion was only modest. Second, dietary